早期光疗对早产儿黄疸的影响

目的：探讨在经皮胆红素监测下早期蓝光干预对早产儿高胆红素血症的防治作用。方法：选择2009年10月-2011年10月我院新生儿科收治的86例出生体重≤2000g,无出生窒息史的早产儿,按住院号单双号分为观察组46例和对照组40例。对照组按照我国2000年制定的新生儿黄疸干预推荐方案的干预标准进行光疗。观察组于出现黄疸和／或经皮胆红素〉85．50μmol／L,但尚未达方案的干预标准就进行光疗,监测经皮胆红素至黄痘消失。经皮胆红素值达187．5μmol／L以上时同时查静脉血监测血清总胆红素。比较2组早产儿经皮胆红素峰值及恢复正常时间。结果：观察组与对照组比较经皮胆红素峰值较低,黄疸持续时间较短,两组比较P均〈0．05,有统计学差异。结论：早产儿在经皮胆红素监测下进行早期蓝光干预有利于降低早产儿胆红素峰值,缩短黄疸持续时间。有效预防早产儿胆红素脑病。     

门冬氨酸鸟氨酸注射液联合乳果糖对肝性脑病患者肝功能和炎性因子水平的影响

目的:探讨门冬氨酸鸟氨酸注射液联合乳果糖对肝性脑病(HE)患者肝功能和炎性因子水平的影响。方法:选取2014年1月～2018年1月期间广西医科大学附属柳铁中心医院收治的HE患者120例为研究对象。根据数字表法将患者随机分为对照组(n=60)和研究组(n=60),对照组给予乳果糖治疗,研究组在对照组基础上联合门冬氨酸鸟氨酸注射液治疗,两组患者均持续治疗14 d。比较两组患者治疗后临床疗效,以及两组患者治疗前后肝功能、炎性因子水平、血尿淀粉酶(AMY)、血氨浓度。记录两组患者治疗期间不良反应发生情况。结果:研究组患者治疗后总有效率为91.67%(55/60),显著高于对照组患者的63.33%(38/60)(P0.05)。两组患者治疗后谷丙转氨酶(ALT)、总胆红素(TBIL)、天冬氨酸转氨酶(AST)水平均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后血清白介素-6(IL-6)、白介素-8(IL-8)、白介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)水平均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后血AMY、尿AMY、血氨浓度均较治疗前降低,且研究组血氨浓度低于对照组(P0.05),但研究组血AMY、尿AMY与对照组比较差异无统计学意义(P0.05)。两组患者治疗期间不良反应率比较差异无统计学意义(P0.05)。结论:门冬氨酸鸟氨酸注射液联合乳果糖治疗HE患者安全有效,可有效改善患者肝功能,减轻炎性应激,降低血尿AMY、血氨浓度,具有一定的临床应用价值。     

The role of exosomes in the processing of proteins associated with neurodegenerative diseases

Exosomes are small membranous vesicles secreted by a number of cell types and can be isolated from conditioned cell media or bodily fluids such as urine and plasma. Exosome biogenesis involves the inward budding of multivesicular bodies (MVB) to form intraluminal vesicles (ILV). When fused with the plasma membrane, the MVB releases the vesicles into the extracellular environment as exosomes. Proposed functions of these vesicles include roles in cell–cell signalling, removal of unwanted proteins, and the transfer of pathogens between cells, such as HIV-1. Another such pathogen which exploits this pathway is the prion, the infectious particle responsible for the transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Interestingly, this work is mirrored by studies on another protein involved in neurodegenerative disease, the amyloid precursor protein (APP) which is associated with Alzheimer’s disease (AD). Recent work has found APP proteolytic fragments in association with exosomes, suggesting a common pathway previously unknown for proteins associated with neurodegenerative diseases. This review will be discussing the current literature regarding the role of exosomes in secretion of the proteins, PrP and APP, and the subsequent implications for neurodegenerative disease. Australian Society for Biophysics Special Issue: Metals and Membranes in Neuroscience.     

pH‐dependent stability of neuroserpin is mediated by histidines 119 and 138; Implications for the control of β‐sheet A and polymerization

Neuroserpin is a member of the serpin superfamily. Point mutations in the neuroserpin gene underlie the autosomal dominant dementia, familial encephalopathy with neuroserpin inclusion bodies. This is characterized by the retention of ordered polymers of neuroserpin within the endoplasmic reticulum of neurons. pH has been shown to affect the propensity of several serpins to form polymers. In particular, low pH favors the formation of polymers of both α₁‐antitrypsin and antithrombin. We report here opposite effects in neuroserpin, with a striking resistance to polymer formation at acidic pH. Mutation of specific histidine residues showed that this effect is not attributable to the shutter domain histidine as would be predicted by analogy with other serpins. Indeed, mutation of the shutter domain His338 decreased neuroserpin stability but had no effect on the pH dependence of polymerization when compared with the wild‐type protein. In contrast, mutation of His119 or His138 reduced the polymerization of neuroserpin at both acidic and neutral pH. These residues are at the lower pole of neuroserpin and provide a novel mechanism to control the opening of β‐sheet A and hence polymerization. This mechanism is likely to have evolved to protect neuroserpin from the acidic environment of the secretory granules.     

Limited role of the c-Jun N-terminal kinase pathway in a neonatal rat model of cerebral hypoxia–ischemia

D-JNKI1, a cell-permeable peptide inhibitor of the c-Jun N-terminal kinase (JNK) pathway, has been shown to be a powerful neuroprotective agent after focal cerebral ischemia in adult mice and young rats. We have investigated the potential neuroprotective effect of D-JNKI1 and the involvement of the JNK pathway in a neonatal rat model of cerebral hypoxia–ischemia (HI). Seven-day-old rats underwent a permanent ligation of the right common carotid artery followed by 2 h of hypoxia (8% oxygen). Treatment with D-JNKI1 (0.3 mg/kg intraperitoneally) significantly reduced early calpain activation, late caspase 3 activation and, in the thalamus, autophagosome formation, indicating an involvement of JNK in different types of cell death: necrotic, apoptotic, and autophagic. However, the size of the lesion was unchanged. Further analysis showed that neonatal HI induced an immediate decrease in JNK phosphorylation (reflecting mainly JNK1 phosphorylation) followed by a slow progressive increase (including JNK3 phosphorylation 54 kDa), whereas c-jun and c-fos expression were both strongly activated immediately after HI. In conclusion, unlike in adult ischemic models, JNK is only moderately activated after severe cerebral HI in neonatal rats and the observed positive effects of D-JNKI1 are insufficient to give neuroprotection. Thus, for perinatal asphyxia, D-JNKI1 can only be considered in association with other therapies.     

Comparison of DNA variants in the PRNP and NF1 regions between bovine spongiform encephalopathy and control cattle

DNA from 252 bovine spongiform encephalopathy (BSE) cattle and 376 non-diseased control cattle were genotyped for nine loci in the prion protein (PRNP) gene region, three loci in the neurofibromin 1 (NF1) region and four control loci on different chromosomes. The allele and genotype frequencies of the control loci were similar in BSE and control cattle. In the analysed 7.4 Mb PRNP region, the largest differences between BSE and control cattle were found for the loci REG2, R16 and R18, which are located between +300 and +5600 bp, spanning PRNP introns 1 to 2. Carriers of the REG2 genotype 128/128 were younger at BSE diagnosis than those with the other genotypes (128/140 or 140/140). The predominant haplotype REG2 128 bp-R18 173 bp occurred more frequently (P < 0.001), and the second-most frequent haplotype (REG2 140 bp-R18 175 bp) occurred less frequently (P < 0.05) in BSE than in control cattle. The largest frequency differences between BSE and control groups were observed in the Brown Swiss breed. Across all breeds, most of the same alleles and haplotypes of the PRNP region were associated with BSE. In the 23-cM NF1 region, associations with BSE incidence were found for the RM222 allele and for the DIK4009 genotype frequencies. Cattle carrying RM222 genotypes with the 127- or 129-bp alleles were about half a year older at BSE incidence than those with other genotypes. Across the breeds, different alleles and genotypes of the NF1 region were associated with BSE. The informative DNA markers were used to localize the genetic disposition to BSE and may be useful for the identification of the causative DNA variants.     

Deer Carcass Decomposition and Potential Scavenger Exposure to Chronic Wasting Disease

ABSTRACT Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy afflicting the Cervidae family in North America, causing neurodegeneration and ultimately death. Although there are no reports of natural cross-species transmission of CWD to noncervids, infected deer carcasses pose a potential risk of CWD exposure for other animals. We placed 40 disease-free white-tailed deer (Odocoileus virginianus) carcasses and 10 gut piles in the CWD-affected area of Wisconsin (USA) from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger visitation and relative activity. To evaluate factors driving the rate of carcass removal (decomposition), we used Kaplan-Meier survival analysis and a generalized linear mixed model. We recorded 14 species of scavenging mammals (6 visiting species) and 14 species of scavenging birds (8 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and Virginia opossums (Didelphis virginiana). We found no evidence that deer consumed conspecific remains, although they visited gut piles more often than carcasses relative to temporal availability in the environment. Domestic dogs, cats, and cows either scavenged or visited carcass sites, which could lead to human exposure to CWD. Deer carcasses persisted for 18 days to 101 days depending on the season and year, whereas gut piles lasted for 3 days. Habitat did not influence carcass decomposition, but mammalian and avian scavenger activity and higher temperatures were positively associated with faster removal. Infected deer carcasses or gut piles can serve as potential sources of CWD prions to a variety of scavengers. In areas where surveillance for CWD exposure is practical, management agencies should consider strategies for testing primary scavengers of deer carcass material.     

The “brave new world” of transmissible spongiform encephalopathy (infectious cerebral amyloidosis)

The story of transmissible human spongiform encephalopathy, from its origins to the present time, enjoys the commentary of a cast of characters from Shakespeare's imaginary island inThe Tempest, with a brief visit to the real island of Tasmania for a bird's eye view of the prion, and some concluding thoughts about the current state of research in the netherworlds of molecular biology and physical chemistry.     

血清心肌酶谱及cTnI对新生儿缺氧缺血性脑病的诊断价值

目的:研究血清心肌酶谱及心肌肌钙蛋白I(c Tn I)对新生儿缺氧缺血性脑病的诊断价值。方法:选取2012年11月到2014年11月我院收治的新生儿缺氧缺血性脑病患儿70例(研究组),另选同期健康新生儿70例(对照组),采用生化仪检测入选者血清心肌酶谱,应用化学发光法检测血清c Tn I,比较两组血清心肌酶谱和c Tn I水平。结果:研究组肌酸激酶(CK)、天门冬氨酸氨基转移酶(AST)、肌酸激酶同工酶(CK-MB)、a-羟丁酸脱氢酶(HBDH)、乳酸脱氢酶(LDH)均显著高于对照组,两组比较差异具有统计学意义(P0.05);研究组c Tn I水平显著高于对照组,两组比较差异具有统计学意义(P0.05);CK-MB检测灵敏度最高,c Tn I检测的特异性最高。结论:血清心肌酶谱及c Tn I对新生儿缺氧缺血性脑病具有重要的诊断价值,为临床治疗提供一定依据。